ARIA: Ambiguous Restraints for Iterative Assignment

The assignment of nuclear Overhauser enhancement (NOE) peaks is the most time-consuming step
in the analysis of nuclear magnetic resonance (NMR) data and structure calculation. Though
several programs exist that facilitate a manual analysis of spectra, the NOE assignment is
tedious due to the large number of assignment possibilities, peak overlap and potential artifacts
in the spectra. Therefore, a widely employed approach to NMR structure determination is to calculate
a structural model from the experimental data by using programs for automated assignment.

Our computer program ARIA (Ambiguous
Restraints for Iterative
Assignment) is a widely used software for automated NOE assignment and NMR
structure calculation. It speeds up and automatizes the assignment process through the use of an iterative
structure calculation scheme. ARIA uses the concept of ambiguous distance restraints (ADR) to automatically
assign NOE cross-peaks. Additionally, a spin-diffusion correction procedure, as well as a refinement in
explicit water improve the quality of the calculated structures. Moreover, ARIA supports the calculation of
symmetric oligomers and protein/protein or protein/nucleic acids complexes.

A graphical user interface (GUI) simplifies and streamlines the setup of a calculation. The GUI enables one to
modify all relevant program parameters, such as the iterative protocol and the simulated annealing schedule, the
shape of the restraining potentials. The program also offers the option to retrieve input data directly from a
CCPN project. This includes details on the molecular system, experimental data such as chemical shifts, NOEs, or
residual dipolar couplings, as well as the results of a calculation, most importantly the assigned spectra
and the 3D coordinates of the structures. We have incorporated the CCPN data model into ARIA to enable spectroscopists
to use existing NMR computer programs in a very efficient way.

Workflow in ARIA: A GUI simplifies the project setup and provides
functionality to analyze the generated assignments. The CCPN data model is
used for data import, and export of assigned spectra and calculated structures.